Abstract
The stem cell pluripotency factor Oct4 serves a critical protective role during atherosclerotic plaque development by promoting smooth muscle cell (SMC) investment. Here, we show using Myh11-CreERT2 lineage-tracing with inducible SMC and pericyte (SMC-P) knockout of Oct4 that Oct4 regulates perivascular cell migration and recruitment during angiogenesis. Knockout of Oct4 in perivascular cells significantly impairs perivascular cell migration, increases perivascular cell death, delays endothelial cell migration, and promotes vascular leakage following corneal angiogenic stimulus. Knockout of Oct4 in perivascular cells also impairs perfusion recovery and decreases angiogenesis following hindlimb ischemia. Transcriptomic analyses demonstrate that expression of the migratory gene Slit3 is reduced following loss of Oct4 in cultured SMCs, and in Oct4-deficient perivascular cells in ischemic hindlimb muscle. Together, these results provide evidence that Oct4 plays an essential role within perivascular cells in injury- and hypoxia-induced angiogenesis.
Highlights
The stem cell pluripotency factor Oct[4] serves a critical protective role during atherosclerotic plaque development by promoting smooth muscle cell (SMC) investment
We demonstrate that SMC and pericyte (SMC-P) conditional deletion of the stem cell pluripotency factor Oct[4] results in markedly impaired angiogenesis, at least in part through defective SMC-P migration leading to increased vascular leak
Our results demonstrate that the Myh11-CreERT2 system labels both SMC22 and a large subset of pericytes within multiple tissues
Summary
The stem cell pluripotency factor Oct[4] serves a critical protective role during atherosclerotic plaque development by promoting smooth muscle cell (SMC) investment. Transcriptomic analyses demonstrate that expression of the migratory gene Slit[3] is reduced following loss of Oct[4] in cultured SMCs, and in Oct4-deficient perivascular cells in ischemic hindlimb muscle Together, these results provide evidence that Oct[4] plays an essential role within perivascular cells in injury- and hypoxia-induced angiogenesis. We found that Oct[4] plays a critical protective role in SMC, in that Oct[4] deletion impaired investment of SMC into both the lesion and fibrous cap during atherosclerosis, and was associated with increased atherosclerotic burden and decreased indices of plaque stability[5] Of major significance, this was the first direct evidence that Oct[4] plays a functional role in any somatic cell. Perivascular cellselective knockout of Ephrin-B212, CD14613, Tie[214], and VEGFR115 result in impaired angiogenesis, including defective
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
